TR New / Reuters

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Unlocking Alzheimer's

Can IGF-1—the “fountain of youth” hormone—be used to slow the aging process, and thus prevent the onset of Alzheimer’s disease? Hannah Seligson talks to the researchers behind a groundbreaking new study.

12.10.09 11:52 PM ET

Researchers at the Salk Institute for Biological Studies in San Diego have made one of the biggest breakthroughs in anti-aging and Alzheimer’s research in the last 40 years: They’ve discovered a way to use hormone pathways to slow the aging process in the brains of mice, and they hope the technique could lead to the development of drugs both to prevent and treat Alzheimer’s disease in humans.

Instead of studying the disease itself, the Salk Institute researchers, led by Andrew Dillin, a professor in the Salk Molecular and Cell Biology Laboratory, targeted age, the main risk factor for Alzheimer’s disease. Beyond the age of 65, the number of people with Alzheimer’s doubles every five years. According to the National Institutes of Health, between 2.4 million and 4.5 million Americans are living with Alzheimer’s. The exact number is difficult to determine, as many people in the early stages of the disease have not been diagnosed.

“The gene that controls lifespan and aging can be enhanced to prevent symptoms of Alzheimer’s disease.”

The scientists at the Salk Institute focused on IGF-1 (insulin-like growth factor 1), which has been called the fountain of youth hormone and has been found to extend life expectancy in humans, worms, and mice. IGF-1 functions as a mediator for human growth hormone (HGH), which plays a critical role in the aging process. HGH promotes tissue repair and cell regeneration in the bones, supports the immune system in combating infection and disease, and ensures that as cells die off, healthy replacements are on hand. In other words, HGH is a factory of health and vitality. But as we age, our HGH level declines, and old cells cannot be replaced as readily with new ones. The body’s ability to self-repair is impaired. This is called aging.

When a mouse’s IGF-1 pathway is tinkered with in the lab, it lives up to 35 percent longer than normal mice. And three studies of centenarians—people who live to be 100—found that they carry mutations of the IGF-1 signal pathway that protect them from the aging process. By activating the IGF-1 gene, the Salk researchers slowed the aging process in one group of mice and left another group of mice to age normally. They then tested the memory and cognitive functioning of each group. The mice were put into a milky water maze that had visual clues on the wall leading them to a submerged platform. The chronically old but biologically young mice—the ones who had their IGF-1 pathways adjusted—were able to find the platform, while the normal aging mice kept swimming around and around, indicating they had significantly more memory erosion than the mice whose aging processes had not been slowed. The brains of the normal mice were becoming noticeably weaker as they aged.

“The Dillin paper is a paradigm shift,” said Dr. Richard Morimoto, director of the Rice Institute for Biomedical Research and a professor of biology at Northwestern University. “It reveals the gene that controls lifespan and aging can be enhanced to prevent symptoms of Alzheimer’s disease,” he told The Daily Beast. “The key point here is that biology can be used to correct the disease.”

The implications of this research are potentially huge. Every 72 seconds, someone in the U.S. develops Alzheimer’s disease, according to a 2007 report by the Alzheimer’s Association. “The fact that it works in a mouse is a very good sign that it will work in a human,” said Dillin. “The IGF-1 receptor is convertible to humans.”

This finding holds potential for all types of Alzheimer’s patients, from those who have early onset in their 40s and 50s to those with a family history of the disease. “There is still an aging component to the disease in both those cases,” Dillin said.

What’s also promising on the genetic front is the mice that were experimented on had the human mutation for Alzheimer’s disease. “In that sense, the mice are a lot more like a familial case than a sporadic case,” he said.

Dillin is already working with a drug company on developing both preventive and treatment drugs for Alzheimer’s disease, based on his recent research. The professor, who cut his teeth as a geneticist at the University of California, Berkeley, said he had always wanted to go after a complex trait, something that had both a biological and genetic component. “Originally I thought I would go after schizophrenia, because it was debated whether it was controlled at the genetic level,” he said in an interview with The Daily Beast.

“But then I found out the IGF-1 gene could be mutated to make a worm live twice as a long,” he said. “The notion that a single gene could change the aging process was very intriguing to me.”

The Dillin paper also challenges other conventional wisdom about the nature of Alzheimer’s disease. Until this study, it was thought that Alzheimer’s disease was caused by beta amyloid, the plaque that has been found Alzheimer patients’ brains. However, Dillin’s experiment found that both normally aging and IGF-1 modified mice had plaque buildup.

“The difference was that in the mice that had their aging process slowed, the plaque was tightly compacted, taking up less space,” Dillin explained. “The long-held belief that plaque causes Alzheimer’s disease might not be true. The structure of the plaque might be more important than its existence.”

And it looks like this could just be the tip of the aging iceberg. “We are definitely going to look at other aging pathways and see how they affect diseases like Parkinson’s and Lou Gehrig’s disease,” Dillin said.